A Crossover Study to Evaluate Relative Bioavailability of Simeprevir Age-appropriate Oral Formulation Candidates Compared With 150-milligram (mg) Oral Capsule in Healthy Adult Participants

Healthy Clinical Trial

Official title:

A Phase 1, Open-label, Randomized, 2-panel, 3-way Crossover Study in Healthy Adult Subjects to Assess the Relative Bioavailability of Simeprevir Following Single Dose Administration of Age-appropriate Oral Formulation Candidates, Compared to the 150-mg Oral Capsule, and to Assess the Effect of Food on the Bioavailability of Simeprevir Following Single Dose Administration of a Selected Age-appropriate Oral Formulation Candidate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02385071
• Other study ID #: CR106516
• Secondary ID: TMC435HPC1010201
• Status: Completed
• Phase: Phase 1
• First received: March 5, 2015
• Last updated: September 4, 2017
• Start date: April 28, 2015
• Est. completion date: September 9, 2015

Study information

• Verified date: September 2017
• Source: Janssen Sciences Ireland UC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the relative bioavailability (the extent to which a drug or other substance becomes available to the body) of simeprevir (SMV) following single dose administration of age-appropriate oral formulation candidates compared to the 150 milligram (mg) capsule, and to assess the effect of food on the bioavailability of SMV following single dose administration of a selected age-appropriate oral formulation candidate.

Description:

This is a Phase 1, open-label (all people know the identity of the intervention), randomized (study medication assigned to participants by chance), 2-panel, 3-way crossover (participants will receive different interventions sequentially during the trial) study in healthy adult participants. Participants will be equally divided over 2 panels, and will not be randomized between panels. Participants will not be allowed to switch panels. The study consists of 3 parts: Screening Phase (that is, 28 days before study commences on Day 1); Open-label Treatment (in subsequent 3-treatment periods in each Panel, each separated with washout period of 7 days); and Post-Treatment Phase (up to 7 days after last study drug intake). The duration of the study per participant will be at least 19 days, screening and follow-up not included. All the eligible participants will be randomly assigned to 1 of the 6 treatment sequences in each Panel. In fasted conditions, study drug will be administered following a 10-hour overnight fast. In fed conditions, participants will also fast from food for 10 hours, but will consume a high fat/high calorie breakfast within a 30-minute period. Study drug will be administered 30 minutes after the start of breakfast. Participants will not be allowed to have food until at least 4 hours after study drug administration. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Relative bioavailability of SMV formulations will be evaluated primarily. Participants' safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: September 9, 2015
• Est. primary completion date: September 9, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Participants must be healthy on the basis of physical examination, medical history, 12-lead electrocardiogram (ECG) and vital signs performed at screening (after signing the ICF), and on Day -1 of the first treatment session, if applicable. If there are abnormalities, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents

• Participants must be willing and able to adhere to the prohibitions and restrictions specified in the protocol and study procedures

• Female participants, except for postmenopausal women, should have a negative serum pregnancy test at screening

• All female participants should have a negative urine pregnancy test on Day -1 of the first treatment session

• Male participants heterosexually active with a woman of childbearing potential must agree to use two effective methods of birth control and all men must not donate sperm during the study and for at least 30 days after receiving the last dose of study drug

Exclusion Criteria:

• Female participants who are pregnant or breast feeding at screening or on Day -1 of the first treatment session

• Participants with current hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin [IgM]), or hepatitis B infection (confirmed by hepatitis B surface antigen [HBsAg]), or hepatitis C infection (confirmed by HCV antibody), or human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection

• Participants with a history or evidence of current or past abuse of alcohol, or recreational or narcotic drugs, which in the Investigator's opinion would compromise the participant's safety and/or compliance with the study procedures

• Participants with any history of clinically relevant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticaria

• Participants with known allergies, hypersensitivity, or intolerance to simeprevir (SMV) or any of the excipients

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Treatment A
150 milligram (mg) SMV capsule with water under fed conditions.
• Treatment B
Treatment B (3*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.
• Treatment C
Treatment C (3*50 mg dispersible SMV tablets dispersed in water under fed conditions).
• Treatment D
*50 mg SMV capsules (including 50 mini-tablets of 1 mg each) with water or 3*50 mg dispersible SMV tablets dispersed in water under fed conditions.
• Treatment E
3*50 mg SMV capsules (including 50 mini-tablets of 1 mg each) with water or 3*50 mg dispersible SMV tablets dispersed in water under fasted conditions.
• Treatment F
3*50 mg SMV capsules (including 50 mini-tablets of 1 mg each) with yoghurt or 3*50 mg dispersible SMV tablets dispersed in apple juice under fed conditions.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax) of Simeprevir (SMV)	The Cmax is the maximum observed plasma concentration of SMV.	Baseline up to 72 hours post-administration of study drug
Primary	Time to Reach the Maximum Plasma Concentration (Tmax) of SMV	The Tmax is the time to reach the maximum observed plasma concentration of SMV.	Baseline up to 72 hours post-administration of study drug
Primary	Area Under the Plasma Concentration-Time Curve From 0 to last (AUC[0-last]) Post Dose of SMV	AUC (0-last) from time 0 to the time of the last measurable (non-below quantification limit [BQL]) concentration, calculated by linear-linear trapezoidal summation.	Baseline up to 72 hours post-administration of study drug
Primary	Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of SMV	The AUC (0-infinity) is the area under the plasma concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.	Baseline up to 72 hours post-administration of study drug
Primary	Elimination Rate Constant (Lambda [z]) of SMV	The Lambda (z) determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.	Baseline up to 72 hours post-administration of study drug
Primary	Terminal Half-life (t[1/2]) of SMV	The t(1/2) is defined as 0.693/Lambda (z).	Baseline up to 72 hours post-administration of study drug
Secondary	Number of Participants within Each Category of Taste Questionnaire	Participants will assess the palatability of the SMV formulations by Taste Questionnaire, Question 1 will assess sweetness, bitterness, flavor and overall taste of the formulation; and Question 2 consists of visual analog scale wherein participants will put a cross in the box beneath the scores, corresponding to the 5-point hedonic scale (dislike it very much; dislike it a little; not sure, like it a little, like it very much).	5 to 15 minutes post administration of study drug (up to Day 19)
Secondary	Number of Participants with Adverse Events (AEs) and Serious AEs	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Screening up to follow-up (7 days after last dose administration)